PROJECT SUMMARY Prevalence of whole-genome sequencing and high-quality annotations of the human genome has started to allow exploration of some of the mechanisms of gene regulation on an organismal scale in humans. Until recently, most efforts have focused on examining the effect of variation in protein coding regions on human phenotype. However, with the release of many whole-genome regulatory annotations, both biochemical and genetic, it has started to become possible to assign putative regulatory function to non-coding DNA. This is particularly significant as a majority of human variation associated with disease falls outside of gene bodies. As a resource, RegulomeDB has provided a concise method to assign putative function to variation. The research project aspects of this proposal will expand and support RegulomeDB. We have demonstrated that RegulomeDB has provided a valuable resource to the community. Here we will detail the efforts required to expand the utility of RegulomeDB to take advantage of the vast array of data generated by labs performing high-throughput ?omics research.